Obstructive sleep apnea (OSA) and hypertension are highly associated, particularly among subjects with resistant hypertension. The mechanism, however, by which the two disorders are related, remains obscure. In evaluating subjects with resistant hypertension, we observed that a large percentage subjects diagnosed with primary hyperaldosteronism (PA) were also being diagnosed with OSA. To further examine this relationship, we prospectively determined plasma renin activity and 24-hr urine aldosterone excretion in 114 subjects with resistant hypertension. In addition, subjects completed the Berlin Questionnaire, a validated instrument for identifying subjects at high risk of having OSA. Subjects at high risk of having OSA had lower plasma renin activity, significantly greater 24-hr urinary aldosterone excretion and were 2 times more likely to have been diagnosed with PA than subjects at low-risk of having OSA. Based on the strength of these results, the overall goal of the current proposal is to test the hypothesis that OSA contributes to the development of resistant hypertension by inducing hyperaldosteronism. Specific Aim 1: To test the hypothesis that aldosterone excretion and obstructive sleep apnea (OSA) are positively related in subjects with resistant hypertension, we will a) correlate 24-hr urinary aldosterone excretion, respiratory disturbance index and nocturnal oxygen saturation as determined during full-night polysomnographic evaluation in 190 consecutive subjects referred to UAB for resistant hypertension; and b) compare the prevalence of OSA in hypertensive subjects with confirmed primary hyperaldosteronism (PA) versus non-PA control subjects. Specific Aim 2: To test the hypothesis that obstructive sleep apnea stimulates aldosterone excretion, we will determine the effects of chronic OSA therapy (i.e., continuous positive airway pressure) on 24-hr urinary aldosterone excretion and known and proposed stimuli of aldosterone excretion (renin, ACTH, atrial natriuretic peptide, norepinephrine and endothelin-1) in 120 consecutive hypertensive subjects with newly diagnosed OSA. Subjects found not to have OSA will serve as controls. [unreadable] [unreadable]